Cerebral perfusion pressure (CPP) is the net pressure gradient that drives oxygen delivery to cerebral tissue. It is the difference between the mean arterial pressure (MAP) and the intracranial pressure (ICP). As CPP is a calculated value, MAP and ICP must be measured simultaneously. In research models, anesthetized and acute monitoring is incapable of providing a realistic picture of the relationship between ICP and MAP under physiological and/or pathophysiological conditions. For long-term monitoring of both pressures, the principle of telemetry can be used. The aim of this study was to map changes in CPP and spontaneous behavior using continuous pressure monitoring and video recording for 7 days under physiological conditions (group C - 8 intact rats) and under altered brain microenvironment induced by brain edema (group WI - 8 rats after water intoxication) and neuroprotection with methylprednisolone - MP (group WI+MP - 8 rats with MP 100 mg/kg b.w. applicated intraperitoneally during WI). The mean CPP values in all three groups were in the range of 40-60 mm Hg. For each group of rats, the percentage of time that the rats spent during the 7 days in movement pattern A (standard movement stereotype) or B (atypical movement) was defined. Even at very low CPP values, the standard movement stereotype (A) clearly dominated over the atypical movement (B) in all rats. There was no significant difference between control and experimental groups. Chronic CPP values with correlated behavioral type may possibly answer the question of whether there is a specific, universal, optimal CPP at all.

• MeSH
• intrakraniální tlak * fyziologie   MeSH
• krevní tlak fyziologie   MeSH
• krysa rodu rattus MeSH
• monitorování fyziologických funkcí MeSH
• mozek * MeSH
• mozkový krevní oběh fyziologie   MeSH
• telemetrie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Farrerol (FA) is a traditional Chinese herbal medicine known for its anti-inflammatory and anti-oxidative properties in various diseases. Ferroptosis is an iron-dependent oxidative stress-induced cell death. It is characterized by lipid peroxidation and glutathione depletion and is involved in neuronal injury. However, the role of FA in inhibiting ferroptosis in hypoxic-ischemic encephalopathy (HIE) and its underlying mechanisms are not yet completely elucidated. This study aimed to investigate whether FA could mediate ferroptosis and explore its function and molecular mechanism in HIE. A neonatal rat model of HIE was used, and rats were treated with FA, ML385 (a specific inhibitor of nuclear factor erythroid 2-related factor 2 [Nrf2]), or a combination of both. Neurological deficits, infarction volume, brain water content, pathological changes, and iron ion accumulation in the brain tissues were measured using the Zea-Longa scoring system and triphenyl tetrazolium chloride (TTC), hematoxylin-eosin (HE), and Perls' staining. The expression levels of GSH-Px, MDA, SOD, and ROS in brain tissues were also evaluated. Western blot analysis was performed to analyze the expression of the Nrf2 pathway and ferroptosis-related proteins. The results showed that FA administration significantly reduced neuronal damage, infarct volume, cerebral edema, and iron ion accumulation and inhibited MDA and ROS levels while promoting GSH-Px and SOD levels. FA also increased the expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), Nrf2, and HO-1. Moreover, the combination of ML385 and FA in HIE abolished the FA protective effects. Therefore, the study concludes that FA exerts a neuroprotective effect after HIE by inhibiting oxidative stress and ferroptosis via the Nrf2 signaling pathway.

• MeSH
• faktor 2 související s NF-E2 MeSH
• ferroptóza * MeSH
• glutathion MeSH
• krysa rodu rattus MeSH
• mozková hypoxie a ischemie * farmakoterapie   MeSH
• novorozená zvířata MeSH
• reaktivní formy kyslíku MeSH
• superoxiddismutasa MeSH
• železo MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The severity of tissue hypoxia is routinely assessed by serum lactate. We aimed to determine whether early lactate levels predict outcomes in refractory out-of-hospital cardiac arrest (OHCA) treated by conventional and extracorporeal cardiopulmonary resuscitation (ECPR). METHODS: This study is a post-hoc analysis of a randomized Prague OHCA study (NCT01511666) assessing serum lactate levels in refractory OHCA treated by ECPR (the ECPR group) or conventional resuscitation with prehospital achieved return of spontaneous circulation (the ROSC group). Lactate concentrations measured on admission and every 4 hours (h) during the first 24 h were used to determine their relationship with the neurological outcome (the best Cerebral Performance Category score within 180 days post-cardiac arrest). RESULTS: In the ECPR group (92 patients, median age 58.5 years, 83% male) 26% attained a favorable neurological outcome. In the ROSC group (82 patients, median age 55 years, 83% male) 59% achieved a favorable neurological outcome. In ECPR patients lactate concentrations could discriminate favorable outcome patients, but not consistently in the ROSC group. On admission, serum lactate >14.0 mmol/L for ECPR (specificity 87.5%, sensitivity 54.4%) and >10.8 mmol/L for the ROSC group (specificity 83%, sensitivity 41.2%) predicted an unfavorable outcome. CONCLUSION: In refractory OHCA serum lactate concentrations measured anytime during the first 24 h after admission to the hospital were found to correlate with the outcome in patients treated by ECPR but not in patients with prehospital ROSC. A single lactate measurement is not enough for a reliable outcome prediction and cannot be used alone to guide treatment.

• MeSH
• hypoxie MeSH
• kardiopulmonální resuscitace * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mimotělní membránová oxygenace * MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• zástava srdce mimo nemocnici * terapie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Background: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is one of the most frequently used mechanical circulatory support devices. Distribution of extracorporeal membrane oxygenation flow depends (similarly as the cardiac output distribution) on regional vascular resistance. Arteriovenous fistulas (AVFs), used frequently as hemodialysis access, represent a low-resistant circuit which steals part of the systemic perfusion. We tested the hypothesis that the presence of a large Arteriovenous fistulas significantly changes organ perfusion during a partial and a full Veno-arterial extracorporeal membrane oxygenation support. Methods: The protocol was performed on domestic female pigs held under general anesthesia. Cannulas for Veno-arterial extracorporeal membrane oxygenation were inserted into femoral artery and vein. The Arteriovenous fistulas was created using another two high-diameter extracorporeal membrane oxygenation cannulas inserted in the contralateral femoral artery and vein. Catheters, flow probes, flow wires and other sensors were placed for continuous monitoring of haemodynamics and organ perfusion. A stepwise increase in extracorporeal membrane oxygenation flow was considered under beating heart and ventricular fibrillation (VF) with closed and opened Arteriovenous fistulas. Results: Opening of a large Arteriovenous fistulas (blood flow ranging from 1.1 to 2.2 L/min) resulted in decrease of effective systemic blood flow by 17%-30% (p < 0.01 for all steps). This led to a significant decrease of carotid artery flow (ranging from 13% to 25% after Arteriovenous fistulas opening) following VF and under partial extracorporeal membrane oxygenation support. Cerebral tissue oxygenation measured by near infrared spectroscopy also decreased significantly in all steps. These changes occurred even with maintained perfusion pressure. Changes in coronary artery flow were driven by changes in the native cardiac output. Conclusion: A large arteriovenous fistula can completely counteract Veno-arterial extracorporeal membrane oxygenation support unless maximal extracorporeal membrane oxygenation flow is applied. Cerebral blood flow and oxygenation are mainly compromised by the effect of the Arteriovenous fistulas. These effects could influence brain function in patients with Arteriovenous fistulas on Veno-arterial extracorporeal membrane oxygenation.

• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Astrocytic Aquaporin 4 (AQP4) and Transient receptor potential vanilloid 4 (TRPV4) channels form a functional complex that likely influences cell volume regulation, the development of brain edema, and the severity of the ischemic injury. However, it remains to be fully elucidated whether blocking these channels can serve as a therapeutic approach to alleviate the consequences of having a stroke. METHODS AND RESULTS: In this study, we used in vivo magnetic resonance imaging (MRI) to quantify the extent of brain lesions one day (D1) and seven days (D7) after permanent middle cerebral artery occlusion (pMCAO) in AQP4 or TRPV4 knockouts and mice with simultaneous deletion of both channels. Our results showed that deletion of AQP4 or TRPV4 channels alone leads to a significant worsening of ischemic brain injury at both time points, whereas their simultaneous deletion results in a smaller brain lesion at D1 but equal tissue damage at D7 when compared with controls. Immunohistochemical analysis 7 days after pMCAO confirmed the MRI data, as the brain lesion was significantly greater in AQP4 or TRPV4 knockouts than in controls and double knockouts. For a closer inspection of the TRPV4 and AQP4 channel complex in the development of brain edema, we applied a real-time iontophoretic method in situ to determine ECS diffusion parameters, namely volume fraction (α) and tortuosity (λ). Changes in these parameters reflect alterations in cell volume, and tissue structure during exposure of acute brain slices to models of ischemic conditions in situ, such as oxygen-glucose deprivation (OGD), hypoosmotic stress, or hyperkalemia. The decrease in α was comparable in double knockouts and controls when exposed to hypoosmotic stress or hyperkalemia. However, during OGD, there was no decrease in α in the double knockouts as observed in the controls, which suggests less swelling of the cellular components of the brain. CONCLUSION: Although simultaneous deletion of AQP4 and TRPV4 did not improve the overall outcome of ischemic brain injury, our data indicate that the interplay between AQP4 and TRPV4 channels plays a critical role during neuronal and non-neuronal swelling in the acute phase of ischemic injury.

• Publikační typ
• časopisecké články MeSH

Pacienti s pokročilým diabetes mellitus (DM) 2. typu a zejména ti, co trpí chronickým selháním ledvin, mají častější kognitivní dysfunkci. Bylo pozorováno několik možných mechanismů: glykace proteinů, změny acidobazické rovnováhy, hypoxie i snížená perfuze mozku. Dosavadní data jsou však kontroverzní a vzájemný vztah mezi možnými mechanismy nebyl dosud testován. Vyšetříme 100 pacientů během hemodialýzy a budeme monitorovat perfúzi mozku, cerebrální oxymetrii, echokardiografii, průtok cévním zkratem a plejádu laboratorních vyšetření. Současně bude provedena průřezová studie o 100 jiných jedinců v různém stádiu chronického onemocnění ledvin, s DM nebo bez něj. Očekáváme časovou souvislost mezi změnami stanovenými uvedenými metodami. Pochopení mechanismů vedoucích ke kognitivní dysfunkci může pomoci zabránit rozvoji tohoto problému u DM a u dialyzovaných pacientů. Může mezi ně patřit podání kyslíku během hemodialýzy nebo snížení průtoku dialyzačním zkratem, těsnější kontrola DM apod.; Advanced type 2 diabetes mellitus patients and especially those with end-stage renal disease (ESRD) frequently suffer from cognitive dysfunction. Several possible mechanisms were suggested: advanced protein glycation, acid-base disturbances, brain hypoxia and decreased cerebral perfusion after hemodialysis. Nevertheless, data are controversial and their interrelationship remains unknown. We will examine 100 patients during hemodialysis and monitor them cerebral perfusion, cerebral oxymetry, echocardiography, dialysis access flow volume calculation and extended lab. Simultaneously, a cross-sectional study counting another 100 patients with ESRD or milder stage of chronic kidney disease will be included into a similar cross-sectional study. We expect time relationship between changes observed by the used methods. Understanding the mechanisms may lead to procedures that could prevent cognitive dysfunction in dialysis patients. Theoretically, they may include oxygen administration during hemodialysis, reduction of dialysis access flow volume, tighter diabetes mellitus control etc.

• MeSH
• chronická renální insuficience komplikace   MeSH
• diabetes mellitus 2. typu komplikace   MeSH
• dialýza ledvin metody   MeSH
• echokardiografie metody   MeSH
• hypoxie komplikace   MeSH
• kognitivní dysfunkce etiologie   MeSH
• komplikace diabetu etiologie   MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• nefrologie
• diabetologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

V současné době je kladen důraz na neinvazivní monitorování orgánových dysfunkcí u kriticky nemocných novorozenců. Bed-side monitoring pomocí spektroskopie (near-infrared spectroscopy, NIRS) nám může poskytnout cenné informace o hemodynamických poruchách, které jsou významně spojeny s neurologickými morbiditami a zvýšenou mortalitou u těchto pacientů. NIRS hodnotí cerebrální perfuzi a oxygenaci a ve spojení s jinými zobrazovacími metodami (funkční echokardiografie), klinickým vyšetřením (srdeční akce, krevní tlak, diuréza, kapilární návrat) a biochemickými parametry (acidobazická rovnováha, hodnota laktátu) může poskytnout celistvější představu o tkáňové perfuzi. Na základě těchto vyšetření můžeme optimalizovat terapii a snížit mortalitu a závažné neurologické morbidity, které zásadním způsobem determinují následný život dítěte.

Non-invasive monitoring of sick infants in the neonatal intensive care unit has become an important part of modern care. Bed-side monitoring using near-infrared spectroscopy (NIRS) could provide valuable pieces of information about hemodynamic disturbances that are significantly associated with neurologic morbidities and increased mortality in vulnerable newborns. NIRS evaluates cerebral perfusion and oxygenation, and in conjunction with other imaging methods (functional echocardiography), clinical assessment (heart rate, blood pressure, urine output, capillary refill time) and biochemical parameters (acid-base homeostasis, lactate level) may give us a more complete picture about tissue perfusion. These tools could help us optimize therapy and reduce mortality and incidence of severe neurologic morbidities that significantly impair long-term outcome.

• MeSH
• blízká infračervená spektroskopie * metody   MeSH
• hemodynamické monitorování MeSH
• hemodynamika MeSH
• intenzivní péče o novorozence * metody   MeSH
• lidé MeSH
• mozkový krevní oběh MeSH
• novorozenec MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• přehledy MeSH

Introduction: Rapid environmental changes, such as successive hypoxic-hypoxic orthostatic challenges (SHHOC) occur in the aerospace environment, and the ability to remain orthostatically resilient (OR) relies upon orchestration of physiological counter-responses. Counter-responses adjusting for hypoxia may conflict with orthostatic responses, and a misorchestration can lead to orthostatic intolerance (OI). The goal of this study was to pinpoint specific cardiovascular and oxygenation factors associated with OR during a simulated SHHOC. Methods: Thirty one men underwent a simulated SHHOC consisting of baseline (P0), normobaric hypoxia (Fi02 = 12%, P1), and max 60 s of hypoxic lower body negative pressure (LBNP, P2). Alongside anthropometric variables, non-invasive cardiovascular, central and peripheral tissue oxygenation parameters, were recorded. OI was defined as hemodynamic collapse during SHHOC. Comparison of anthropometric, cardiovascular, and oxygenation parameters between OR and OI was performed via Student's t-test. Within groups, a repeated measures ANOVA test with Holm-Sidak post hoc test was performed. Performance diagnostics were performed to assess factors associated with OR/OI (sensitivity, specificity, positive predictive value PPV, and odd's ratio OR). Results: Only 9/31 were OR, and 22/31 were OI. OR had significantly greater body mass index (BMI), weight, peripheral Sp02, longer R-R Interval (RRI) and lower heart rate (HR) at P0. During P1 OR exhibited significantly higher cardiac index (CI), stroke volume index (SVI), and lower systemic vascular resistance index (SVRI) than OI. Both groups exhibited a significant decrease in cerebral oxygenation (TOIc) with an increase in cerebral deoxygenated hemoglobin (dHbc), while the OI group showed a significant decrease in cerebral oxygenated hemoglobin (02Hbc) and peripheral oxygenation (TOIp) with an increase in peripheral deoxygenated hemoglobin (dHbp). During P2, OR maintained significantly greater CI, systolic, mean, and diastolic pressure (SAP, MAP, DAP), with a shortened RRI compared to the OI group, while central and peripheral oxygenation were not different. Body weight and BMI both showed high sensitivity (0.95), low specificity (0.33), a PPV of 0.78, with an OR of 0.92, and 0.61. P0 RRI showed a sensitivity of 0.95, specificity of 0.22, PPV 0.75, and OR of 0.99. Delta SVI had the highest performance diagnostics during P1 (sensitivity 0.91, specificity 0.44, PPV 0.79, and OR 0.8). Delta SAP had the highest overall performance diagnostics for P2 (sensitivity 0.95, specificity 0.67, PPV 0.87, and OR 0.9). Discussion: Maintaining OR during SHHOC is reliant upon greater BMI, body weight, longer RRI, and lower HR at baseline, while increasing CI and SVI, minimizing peripheral 02 utilization and decreasing SVRI during hypoxia. During hypoxic LBNP, the ability to remain OR is dependent upon maintaining SAP, via CI increases rather than SVRI. Cerebral oxygenation parameters, beyond 02Hbc during P1 did not differ between groups, suggesting that the during acute hypoxia, an increase in cerebral 02 consumption, coupled with increased peripheral 02 utilization does seem to play a role in OI risk during SHHOC. However, cardiovascular factors such as SVI are of more value in assessing OR/OI risk. The results can be used to implement effective aerospace crew physiological monitoring strategies.

• Publikační typ
• časopisecké články MeSH

Alterations in brain functioning, especially in regions associated with cognition, can result from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and are predicted to result in various psychiatric diseases. Recent studies have shown that SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) can directly or indirectly affect the central nervous system (CNS). Therefore, diseases associated with sequelae of COVID-19, or 'long COVID', also include serious long-term mental and cognitive changes, including the condition recently termed 'brain fog'. Hypoxia in the microenvironment of select brain areas may benefit the reproductive capacity of the virus. It is possible that in areas of cerebral hypoxia, neuronal cell energy metabolism may become compromised after integration of the viral genome, resulting in mitochondrial dysfunction. Because of their need for constant high metabolism, cerebral tissues require an immediate and constant supply of oxygen. In hypoxic conditions, neurons with the highest oxygen demand become dysfunctional. The resulting cognitive impairment benefits viral spread, as infected individuals exhibit behaviors that reduce protection against infection. The effects of compromised mitochondrial function may also be an evolutionary advantage for SARS-CoV-2 in terms of host interaction. A high viral load in patients with COVID-19 that involves the CNS results in the compromise of neurons with high-level energy metabolism. Therefore, we propose that selective neuronal mitochondrial targeting in SARS-CoV-2 infection affects cognitive processes to induce 'brain fog' and results in behavioral changes that favor viral propagation. Cognitive changes associated with COVID-19 will have increasing significance for patient diagnosis, prognosis, and long-term care.

• MeSH
• COVID-19 komplikace   metabolismus   patofyziologie   psychologie   přenos   MeSH
• energetický metabolismus MeSH
• kognitivní dysfunkce metabolismus   patofyziologie   psychologie   MeSH
• lidé MeSH
• mikrobiální viabilita MeSH
• mitochondrie metabolismus   MeSH
• mozková hypoxie metabolismus   patofyziologie   psychologie   MeSH
• neurony metabolismus   MeSH
• replikace viru MeSH
• SARS-CoV-2 fyziologie   MeSH
• virová nálož MeSH
• zdravé chování * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• úvodníky MeSH

Ve druhé polovině 20. století byl jedním z ústředních témat vývojové fyziologie problém „vysoké odolnosti novorozených savců vůči kyslíkové nedostatečnosti“. Soustředilo se na něj několik tehdejších předních pracovišť. Článek přináší hlavní experimentální výsledky pracoviště autora, které by mohly inspirovat i současný výzkum.Rozsáhlá série pokusů na mláďatech potkanů naznačila existenci velmi účinného mechanismu, jenž umožňuje novorozeným savcům odolat nedostatku kyslíku. Základem přežití v hypoxickém prostředí (ve stavu kyslíkové nouze) je schopnost nezralé tkáně (nediferencované a dosud nenastavené na homeostatické podmínky při současné absenci regulačních mechanismů) snížit závislost organismu na oxidačních procesech. U nezralého organismu závisí spotřeba na podmínkách prostředí, kdy nabídka kyslíku určuje míru jeho utilizace. Jedním z mechanismů odolnosti novorozeného mozku vůči hypoxii by mohla být i zvýšená efektivita fosforylace, tj. spřaženosti oxidačních dějů s pochody tvorby ATP, která byla pozorována jak na úrovni homogenátu mozkové tkáně, tak na úrovni mitochondrií. Kyslíková nedostatečnost v experimentálních podmínkách na potkanech, ale i v paralelním pozorování u lidských novorozenců vedla k vzestupu zastoupení PUFA omega-3. To by mohlo být interpretováno jako lipogenetický proces, realizovaný elongačními a doprovázený desaturačními pochody v řadě mastných kyselin PUFA omega-3.

In the second half of the 20th century, one of the central themes of developmental physiology was the problem of “high resistance of newborn mammals to oxygen insufficiency.” Several leading laboratories at the time studied the question. The article presents the main experimental results of the author's research group, which could also inspire the current research. An extensive series of experiments on rat pups has indicated the existence of a very effective mechanism that allows newborn mammals to withstand a lack of oxygen. The basis of survival in a hypoxic environment (in a state of oxygen emergency) is the ability of immature tissue (undifferentiated and not yet adjusted to homeostatic conditions in the current absence of regulatory mechanisms), to reduce the body's dependence on oxidative processes. In the immature organism, consumption depends on envi-ronmental conditions, where the supply of oxygen determines the degree of its utilization.One of the mechanisms of resistance of the newborn brain to hypoxia could be the increased efficiency of phosphorylation, i.e. the association of oxidative processes with the processes of ATP production, which was observed both at the level of brain tissue homogenate and at the level of mitochondria.Oxygen deficiency in experimental conditions in rats, but also in parallel observations in human neonates, led to an increase in the proportion of PUFA omega-3. This could be interpreted as a lipogenetic process carried out by elongation and accompanied by desaturation processes in a number of PUFA omega-3 fatty acids..

• MeSH
• hypoxie * patofyziologie   MeSH
• lipogeneze fyziologie   MeSH
• mitochondrie fyziologie   MeSH
• modely u zvířat MeSH
• mozková kůra fyziologie   růst a vývoj   MeSH
• novorozená zvířata * fyziologie   růst a vývoj   MeSH
• odolnost vůči nemocem fyziologie   MeSH
• potkani Wistar fyziologie   růst a vývoj   MeSH
• savci fyziologie   růst a vývoj   MeSH
• spotřeba kyslíku MeSH
• statistika jako téma MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH